Li Jiang, Liu Kai, Sheng Yuehong, Zhang Qin, Chen Lei, Qian Haihua, Wu Hongping, Su Changqing
Department of Molecular Oncology, National Center for Liver Cancer, Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai 200438, P.R. China.
Department of Biliary Tract Surgery IV, Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai 200438, P.R. China.
Oncol Lett. 2020 Dec;20(6):299. doi: 10.3892/ol.2020.12162. Epub 2020 Sep 28.
Cancer stem cells are considered to be tumor-initiating cells. To explain the initiation or progression of hepatocellular carcinoma (HCC), we previously established a culture system that may enrich hepatic cancer stem-like cells (HCSCs). However, the regulatory mechanisms by which HCSCs acquire stem cell properties remain unclear. In the present study, three pairs of HCSCs and case-matched human HCC cells were analyzed by high-throughput screening, and novel biomarkers and pathways for the regulation of HCSCs were identified. The results led to the identification and stratification of 406 differentially expressed genes (DEGs), among which 73 GO terms were found to be significantly associated with DEGs in HCSCs, and only complement and coagulation cascade pathways were identified during the development of HCSCs. By combining the results of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, it was revealed that 7 genes were downregulated in the complement and coagulation cascade pathways, and 7 miRNAs were predicted to target several downregulated genes involved in these pathways. The results may contribute toward hepatic cancer stem cell studies and novel drug research for HCC treatment.
癌症干细胞被认为是肿瘤起始细胞。为了解释肝细胞癌(HCC)的起始或进展,我们之前建立了一种可能富集肝癌干细胞样细胞(HCSCs)的培养系统。然而,HCSCs获得干细胞特性的调控机制仍不清楚。在本研究中,通过高通量筛选分析了三对HCSCs和病例匹配的人肝癌细胞,并鉴定了调控HCSCs的新生物标志物和途径。结果导致鉴定和分层了406个差异表达基因(DEGs),其中73个基因本体(GO)术语被发现与HCSCs中的DEGs显著相关,并且在HCSCs发育过程中仅鉴定出补体和凝血级联途径。通过结合基因本体和京都基因与基因组百科全书分析的结果,发现补体和凝血级联途径中有7个基因下调,并且预测有7个微小RNA(miRNAs)靶向参与这些途径的几个下调基因。这些结果可能有助于肝癌干细胞研究和用于HCC治疗的新药研究。